refractory advanced-stage cutaneous T-cell lymphoma: multi-

national phase II-III trial results. J Clin Oncol 2001;19:2456-71.

4. Kwak B, Mulhaupt F, Myit S, Mach F. Statins as a newly

recognized type of immunomodulator. Nat Med 2000;6:1399-

402.

5. Apisarnthanarax N, Duvic M. Cutaneous T-cell lymphoma: New

immunomodulators. In: Thiers BH, Werth VP, Duvic M, editors.

Dermatology Clinics—Medical Dermatology. Philadelphia, PA:

W.B. Saunders Company, 2001. p. 737-48.

doi:10.1016/j.jaad.2003.04.007

Reply

To the Editor:We appreciate the comments of Fraser-Andrews et al relating to our manuscript,1 and wouldlike to address the points of their letter as follows.

It is true that the existing staging system is notbased on multiple lymph node assessment.2 How-ever, this should not deter physicians from trying tobetter characterize the extent of disease by using

J AM ACAD DERMATOL

VOLUME 51, NUMBER 3

Letters 483

Should multiple lymph node biopsiesbe taken?

To the Editor: We read with interest the study byBreneman et al,1 which concludes that histopatho-logic analysis of multiple lymph nodes (LN) may al-low more accurate staging and therefore prognosisof patients with mycosis fungoides (MF). However,we would like to add several provisos to this claim.

First, the existing staging system is not based onmultiple LN assessment,2 and the prognosis based onsingle LN biopsy may not apply. Considerationwould have to be given as to whether the nodeswere taken from the same or different LN chains, forexample.

Second, additional information regarding tumorburden may be gained by T-cell receptor (TCR) geneanalysis of the biopsied node rather than additionalLN biopsy. Clonal T-cell populations have beendemonstrated in dermatopathic LN, and the detec-tion of a T-cell clone has prognostic implications,3-5

although this is not yet included in the stagingsystem. The authors note this in their study, and alsothat a T-cell clone is not always found in a LN,particularly with early involvement.

We disagree, however, that histopathologic anal-ysis samples a larger proportion of the biopsied LNthan TCR gene analysis; we routinely extract DNAfrom at least a quarter of the excised LN. Intuitively, italso seems unlikely that the section sampled forhistopathological analysis is different to the sectionsampled for TCR gene analysis. A more likely expla-nation is that the previously published studies useSouthern blot analysis to perform TCR gene re-arrangement studies, which has a detection sensi-tivity of approximately 5%.

Using the more sensitive technique of PCR/singlestrand polymorphism analysis (0.5%)6 we havedetected a clonal T-cell population in 18 of 33patients with MF, including 5 of 19 with de-rmatopathic changes and only occasional or smallclusters of atypical lymphocytes (LN0-2).7 Of these19 patients the clonal cases have a worse prognosisof 23 months from LN biopsy compared with greater

than 46 months in the non-clonal cases (follow-up 6-72 months, unpublished data).

Thus we would not routinely advocate multipleLN biopsies at present; clearly more data than the 8patients included in this study is required. We wouldinstead suggest TCR gene analysis be performed onthe already excised node to gain additional informa-tion and avoid further patient morbidity.

Elisabeth Fraser-AndrewsSean Whittaker

Robin Russell-Jones

Skin Tumour UnitSt. John’s Institute of Dermatology

St. Thomas’ HospitalLambeth Palace RoadLondon SE1 7EH, UK

REFERENCES

1. Breneman DL, Raju US, Breneman JC, Steele PE, McFadden DW,

Cualing HD, et al. Lymph node grading for staging of mycosis

fungoides may benefit from examination of multiple excised

lymph nodes. J Am Acad Dermatol 2003;43:702-6.

2. Bunn PA, Lamberg SI. Report of the Committee on staging and

classification of cutaneous T-cell lymphomas. Cancer Treat Rep

1979;63:725-8.

3. Bakels V, van Oostveen JW, Geerts ML, Gordijn RL, Walboomers

JM, Scheffer E, et al. Diagnostic and prognostic significance of

clonal T-cell receptor beta gene rearrangements in lymph

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249-55.

4. Kern DE, Kidd PG, Moe R, Hanke D, Olerud JE. Analysis of T-cell

receptor gene rearrangement in lymph nodes of patients with

mycosis fungoides: Prognostic implications. Arch Dermatol

1998;134:158-64.

5. Lynch JW Jr, Linoilla I, Sausville EA, Steinberg SM, Ghosh BC,

Nguyen DT, et al. Prognostic implications of evaluation for

lymph node involvement by T-cell antigen receptor gene

rearrangement in mycosis fungoides. Blood 1992;79:3293-9.

6. Fraser-Andrews EA, Woolford AJ, Russell-Jones R, Seed PT,

Whittaker SJ. Detection of a peripheral blood T-cell clone is an

independent prognostic marker in mycosis fungoides. J Invest

Dermatol 2000;114:117-21.

7. Sausville EA, Worsham GF, Matthews MJ, Makuch RW, Fisch-

mann AB, Schechter GP, et al. Histologic assessment of lymph

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lymphoma): Clinical correlations and prognostic import of a new

classification system. Hum Pathol 1985;16:1098-109.

doi:10.1016/j.jaad.2003.12.045